Carboxymethylcellulose polyethylene glycol compositions for medical uses

Abstract

Compositions and method of manufacturing carboxypolysaccharides (CPS) including carboxymethyl cellulose (CMC) and polyethylene glycols (PEGs) are provided where the PEG is a PEG-epoxide covalently linked to the CPS. In certain embodiments, the PEG attaches to only one CPS, forming a decorated CPS. In other embodiments, the functional groups of a bi-functional PEG molecule (PEG diglycidyl ether) are attached to different CPSs, thereby forming a covalently cross-linked composition. Such compositions can be used as space-filling materials, load-bearing materials, anti-adhesion compositions, drug delivery vehicles, and lubricants of tissues and medical instruments.

We claim: 
     
       1. A biologically compatible PEG/CMC gel composition being suitable for inhibiting formation or reformation of adhesions after surgery, for space filling, or for lubrication, comprising:
 a carboxymethyl cellulose (CMC) having an average molecular weight of about 700 kD (CMC-A) and a degree of substitution of about 0.65 to 0.85; and 
 a polyethylene glycol di-epoxide (PEG diglycidyl ether (PEGDGE)) having a molecular weight between about 500 Daltons and about 8000 Daltons, said PEG linked to said CMC-A via an addition reaction of one of said epoxide moieties of said PEGDGE to a carboxyl or a hydroxyl moiety of one molecule of CMC-A, and the other of said epoxide moieties of said PEGDGE to a carboxyl or a hydroxyl moiety of another molecule of CMC-A in the presence of 0.01% citric acid, forming a cross-linked PEG/CMC-A gel composition having a carboxymethyl anhydroglucose unit (CMAG) to epoxide (EP) ratio of about 14.3, said gel composition having a pH of about 6.8, and being suitable for inhibiting formation or reformation of adhesions after surgery, for space filling, or for lubrication. 
 
     
     
       2. The composition of  claim 1 , further comprising a drug. 
     
     
       3. The composition of  claim 1 , wherein said composition is a membrane, a bead or sponge. 
     
     
       4. The composition of  claim 1 , encased within a biocompatible sac or bag. 
     
     
       5. A method for manufacturing a PEG/CMC gel composition being suitable for inhibiting formation or reformation of adhesions after surgery, for space filling, or for lubrication, comprising the steps:
 selecting a carboxymethyl cellulose (CMC) having an average molecular weight of about 700 kD (CMC-A) and a degree of substitution of about 14.3; and 
 selecting a polyethylene glycol di-epoxide (PEG diglycidyl ether (PEGDGE)) having a molecular weight between about 500 Daltons and about 8000 Daltons; 
 mixing said CMC and said PEGDGE together in aqueous solution in the presence of 0.01% citric acid; 
 permitting a PEG/CMC composition to form, said PEG linked to said CMC-A via an addition reaction of one of said epoxide moieties of the PEGDGE to a carboxyl or a hydroxyl moiety of one molecule of CMC-A, and the other of said epoxide moieties of the PEGDGE to a carboxyl or a hydroxyl moiety of another molecule of CMC-A, forming a cross-linked PEG/CMC-A gel composition having a carboxymethyl anhydroglucose unit (CMAG) to epoxide (EP) ratio of about 14.3, 
 adjusting the pH to about 6.8; and 
 said composition being suitable for inhibiting formation or reformation of adhesions after surgery, for space filling, or for lubrication.